The Dana-Farber Cancer Institute-Physical Sciences-Oncology Center (DFCI-PSOC) will promote the understanding of cancer evolution and treatment responses utilizing approaches from the physical and experimental sciences. The PSOC will assemble and develop a trans- disciplinary team, research and training programs, and infrastructure organized around our physical sciences-based framework to address a fundamental question in cancer research: how can we utilize a quantitative, physical sciences-based understanding of the spatio-temporal aspects tumor evolution and treatment response to improve patient care? Our trans-disciplinary center will develop and test, individually and through collaborative trans-network activities, physical sciences-based experimental and theoretical concepts that complement and advance our current understanding of cancer biology and oncology. Specifically, the DFCI-PSOC aims to (i) Assemble and develop an integrated trans-disciplinary research team that will work closely together to develop and validate mathematical modeling strategies of cancer evolution and treatment response, and utilize these strategies to identify best therapeutic intervention schedules for hematologic, brain and breast malignancies, with the ultimate goal of improving patient care. (ii) Develop and test, individually and through collaborative network activities, strategies for physical sciences-based measurements of single cell behavior of both animal model and human cancer samples, and utilize these measurements to inform mathematical modeling strategies of treatment response in hematologic, brain and breast malignancies. (iii) Integrate physical sciences perspectives into cancer research to complement and expand on our current understanding of cancer across many length-scales and time-scales, with the ultimate goal of improving cancer prevention, detection, diagnosis, prognosis, and therapy. (iv) Disseminate our findings, approaches and methodologies to the PSOC network and the wider scientific community as well as implement education and outreach programs to interact with patients, students, researchers, advocates, and the general public. Together, the approaches and methodologies developed within the DFCI-PSOC will enable us to further our understanding of the physical principles underlying cancer evolution and treatment response with the ultimate goal of designing optimum intervention strategies for hematologic, brain and breast malignancies.